Our major objective is to enhance understanding of the ventilatory control system. Our specific goal is to increase knowledge of the relationship between carotid body (CB) chemoreceptor and CNS ventilatory control mechanisms. We will examine mechanisms of ventilatory acclimatization to chronic hypoxia (VACH), interactions between O2 and CO2 in the CB, and the effects of varying cerebral oxygenation on input from CB chemoreceptors. Two experimental approaches will be used: a) perfusion of the CB in the awake goat using newly developed methods that allow separation and control of arterial blood gases reaching the CB and the brain. b) To complement the above perfusion studies and add new knowledge to the function of the CB, we will do long term (hours) recording of CB afferent activity in anesthetized goats. In the CB perfusion model, vessels supplying one side of the brain are ligated but the brain blood flow which is supplied from the contralateral vessels remains normal. A vascular shunt is inserted in the ligated site carotid artery which allows perfusion of the CB, but not the brain, by an extracorporeal circuit. The other CB is removed. We have found the preparation normally responsive to CB stimulation and have completed a study using the model demonstrating that VACH can occur in the absence of brain hypoxia. The questions we will examine are: a) Is cerebral alkalosis a component of VACH? b) Does non-hypoxic CB stimulation (hypercapnia) induce acclimatization? c) Do time-dependent changes in CB afferent activity occur over hours of hypoxic or hypercapnic CB stimulation? d) Are CB dopamine receptors involved in VACH? e) What are O2 and CO2 interactions at the CB and do they correlate with ventilation in the awake goat? f) How does the level of O2 in the brain influence the ventilatory response to CB stimulation? These studies provide a new approach to some long unanswered questions and will contribute to our knowledge of the separate roles of the brain and CB in ventilatory control. The data obtained will add to our understanding of the pathophysiology of diseases characterized by chronic hypoxia and/or hypercapnia.